Our research interests are related to DNA and the enzymes which act upon DNA, especially DNA polymerase. In a study of the mechanism by which a DNA polymerase acts upon duplex DNA, we developed a method for identifying 3' terminal nucleotide sequences. We have so far applied the method to T7 DNA and lambda DNA, but the method is applicable to any DNA molecule and in another laboratory has been used for a tumor virus DNA. In the case of lambda DNA, our finding that the terminal sequences are rotationally symmetrical has led us to propose a mechanism for the formation of the mature DNA from a concatemer precursor. To test whether terminal rotationally symmetrical sequences are a common property of linear DNAs, we are now investigating the terminal sequences of DNA from other viruses related to lambda and to P2, and from T7 DNA. Because of the great interest in understanding the interaction between proteins and nucleic acid sequences, we are also attempting to isolate the "ter" enzyme which converts a lambda-concatemer into the mature DNA molecules. (This enzyme must bind to the lambda sequence which we have identified). Principles of protein-DNA interaction which are developed from our sequencing studies or from our isolation of the "ter" enzyme may be generally applicable to the DNA of many types of viruses, including those which may cause cancer. We are also studying replication of DNA in two systems. In a bacterial system we have investigated the mechanism by which KCN or CO inhibits DNA synthesis. We found that these reagents block replication by causing depletion of ATP and deoxynucleoside triphosphates. Surprisingly, we found that uncouplers of oxidative phosphorylation strongly inhibit replication but do not affect triphosphates. They appear to inhibit by a novel mechanism, which we are now investigating. We are also studying the exotic mitochondrial DNA in Leishmania tarentolae. This DNA is in the form of tiny circles which are linked together in associations. We are studying the replication of this DNA, the disruption of the associations during segregation of the daughter chromosomes, and the enzymes involved in these processes.